Polymer drug delivery system Dotaz Zobrazit nápovědu
Research and development in health care industry is in persistence progression. To make it more patient-friendly or to get maximum benefits from it, special attention to different advanced drug delivery system (ADDS) is employed that delivers the drug at the target site and will be able to sustain/control release of drugs. ADDS should be non-toxic, biodegradable, biocompatible along with desirable showing physicochemical and functional properties. These drug delivery systems can be totally based on polymers, either with natural or synthetic polymers. The molecular weight of polymer can be tuned and different groups of polymers can be modified or substituted with other functional groups. Degree of substitution is also tailored. Cationic starch in recent years is exploited in drug delivery, tissue engineering and biomedicine. Due to their abundant availability, low cost, easy chemical modification, low toxicity, biodegradability and biocompatibility, extensive research is now being carried out. Our present discussion will shed light on the usage of cationic starch in health care system.
- Klíčová slova
- Advanced drug delivery system, Biocompatibility, Biodegradability, Cationic starch, Health care system,
- MeSH
- kationty chemie MeSH
- lidé MeSH
- polymery * chemie MeSH
- polysacharidy chemie MeSH
- poskytování zdravotní péče MeSH
- škrob * chemie MeSH
- systémy cílené aplikace léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- kationty MeSH
- polymery * MeSH
- polysacharidy MeSH
- škrob * MeSH
The coiled coil is a superhelical structural protein motif that has been thoroughly investigated in recent years. Because of the relatively well-understood principles that determine the properties of coiled coil peptides and proteins, macromolecular systems containing the coiled coil motif have been suggested for various applications. This short review focuses on hybrid polymer coiled coil systems designed for drug delivery purposes. After a short introduction, the most important features of the coiled coils (stability, association number, oligomerization selectivity and orientation of helices) are described, and the factors influencing these characteristics are discussed. Several examples of the most interesting biomedical applications of the polymer-coiled coil systems (according to the authors' opinion) are presented.
- MeSH
- aminokyselinové motivy * MeSH
- hydrogely MeSH
- konformace proteinů MeSH
- molekulární modely MeSH
- rekombinantní proteiny aplikace a dávkování genetika farmakologie MeSH
- rozpustnost MeSH
- systémy cílené aplikace léků metody MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- hydrogely MeSH
- rekombinantní proteiny MeSH
A novel polymeric micellar pH-sensitive system for delivery of doxorubicin (DOX) is described. Polymeric micelles were prepared by self-assembly of amphiphilic diblock copolymers in aqueous solutions. The copolymers consist of a biocompatible hydrophilic poly(ethylene oxide) (PEO) block and a hydrophobic block containing covalently bound anthracycline antibiotic DOX. The starting block copolymers poly(ethylene oxide)-block-poly(allyl glycidyl ether) (PEO-PAGE) with a very narrow molecular weight distribution (Mw/Mn ca. 1.05) were prepared by anionic ring opening polymerization using sodium salt of poly(ethylene oxide) monomethyl ether as macroinitiator and allyl glycidyl ether as functional monomer. The copolymers were covalently modified via reactive double bonds by the addition of methyl sulfanylacetate. The resulting ester subsequently reacted with hydrazine hydrate yielding polymer hydrazide. The hydrazide was coupled with DOX yielding pH-sensitive hydrazone bonds between the drug and carrier. The resulting conjugate containing ca. 3 wt.% DOX forms micelles with Rh(a)=104 nm in phosphate-buffered saline. After incubation in buffers at 37 degrees C DOX was released faster at pH 5.0 (close to pH in endosomes; 43% DOX released within 24 h) than at pH 7.4 (pH of blood plasma; 16% DOX released within 24 h). Cleavage of hydrazone bonds between DOX and carrier continues even after plateau in the DOX release from micelles incubated in aqueous solutions is reached.
- MeSH
- doxorubicin aplikace a dávkování farmakokinetika MeSH
- koncentrace vodíkových iontů MeSH
- micely * MeSH
- polymery aplikace a dávkování farmakokinetika MeSH
- systémy cílené aplikace léků metody MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- doxorubicin MeSH
- micely * MeSH
- polymery MeSH
Chitosan is a natural polymer with acceptable biocompatibility, biodegradability, and mechanical stability; hence, it has been widely appraised for drug and gene delivery applications. However, there has been no comprehensive assessment to tailor-make chitosan cross-linkers of various types and functionalities as well as complex chitosan-based semi- and full-interpenetrating networks for drug delivery systems (DDSs). Herein, various fabrication methods developed for chitosan hydrogels are deliberated, including chitosan crosslinking with and without diverse cross-linkers. Tripolyphosphate, genipin and multi-functional aldehydes, carboxylic acids, and epoxides are common cross-linkers used in developing biomedical chitosan for DDSs. Methods deployed for modifying the properties and performance of chitosan hydrogels, via their composite production (semi- and full-interpenetrating networks), are also cogitated here. In addition, recent advances in the fabrication of advanced chitosan hydrogels for drug delivery applications such as oral drug delivery, transdermal drug delivery, and cancer therapy are discussed. Lastly, thoughts on what is needed for the chitosan field to continue to grow is also debated in this comprehensive review article.
- Klíčová slova
- Chitosan polymer, Composite hydrogels, Cross-linkers, Drug delivery, Hydrogels,
- MeSH
- aldehydy MeSH
- chitosan * MeSH
- epoxidové sloučeniny MeSH
- hydrogely MeSH
- kyseliny karboxylové MeSH
- polymery MeSH
- systémy cílené aplikace léků metody MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- aldehydy MeSH
- chitosan * MeSH
- epoxidové sloučeniny MeSH
- hydrogely MeSH
- kyseliny karboxylové MeSH
- polymery MeSH
Antibody-mediated targeting is an efficient strategy to enhance the specificity and selectivity of polymer nanomedicines towards the target site, typically a tumor. However, direct covalent coupling of an antibody with a polymer usually results in a partial damage of the antibody binding site accompanied with a compromised biological activity. Here, an original solution based on well-defined non-covalent interactions between tris-nitrilotriacetic acid (trisNTA) and hexahistidine (His-tag) groups, purposefully introduced to the structure of each macromolecule, is described. Specifically, trisNTA groups were attached along the chains of a hydrophilic statistical copolymer based on N-(2-hydroxypropyl)methacrylamide (HPMA), and at the end or along the chains of thermo-responsive di-block copolymers based on N-isopropylmethacrylamide (NIPMAM) and HPMA; His-tag was incorporated to the structure of a recombinant single chain fragment of an anti-GD2 monoclonal antibody (scFv-GD2). Static and dynamic light scattering analyses confirmed that mixing of polymer with scFv-GD2 led to the formation of polymer/scFv-GD2 complexes; those prepared from thermo-responsive polymers formed stable micelles at 37 °C. Flow cytometry and fluorescence microscopy clearly demonstrated antigen-specific binding of the prepared complexes to GD2 positive murine T-cell lymphoma cells EL-4 and human neuroblastoma cells UKF-NB3, while no interaction with GD2 negative murine fibroblast cells NIH-3T3 was observed. These non-covalent polymer protein complexes represent a new generation of highly specific actively targeted polymer therapeutics or diagnostics.
- Klíčová slova
- Hydrophilic polymers, Non-covalent attachment, Polymer drug delivery system, Recombinant proteins, Thermo-responsive polymers, Tris(nitrilotriacetic acid) ligation, Tumor-specific targeting,
- MeSH
- kyselina nitrilotrioctová MeSH
- lidé MeSH
- myši MeSH
- nádory * MeSH
- polymery * chemie MeSH
- rekombinantní proteiny MeSH
- systémy cílené aplikace léků metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- hydroxypropyl methacrylate MeSH Prohlížeč
- kyselina nitrilotrioctová MeSH
- polymery * MeSH
- rekombinantní proteiny MeSH
The aim of this study was to develop a multiple-unit dosage system that released model drug into the colon, and also to evaluate the efficiency of the dosage form in human volunteers. The developed system combines pH-, time- and biodegradable polymer-based mechanisms for drug targeting to the colon. Pellet cores containing caffeine as model drug and chitosan and microcrystalline cellulose as excipients were prepared by the extrusion/spheronization method. The prepared pellets were film coated with a pH-dependent polymer, Eudragit FS 30 D. The coating total weight gain was 28.83% (w/w). Thanks to the application of an outer enteric film and the multiple unit design of the dosage form, the variability in gastric emptying was overcome, and a colon-specific targeting relied on the reproducibility of a small intestinal transit time, which was reported to be 3 ± 1 hours. A biodegradable polymer in the pellet core, chitosan, ensured the site-specific release of the model drug due to its solubility at the lower pH of the colonic region and by its biodegradability from the bacteria present. The efficiency of the system was confirmed by the in vivo testing of human saliva. The time of the first appearance of caffeine into the saliva, T(lag), was used as a parameter to estimate the disintegration time of the pellets into the gastrointestinal tract. The caffeine appeared in the saliva within 6.95 ± 1.12 hours (T(lag)) in 9 volunteers. A comparison of the reported colon arrival times indicates that the developed system is applicable to colonic drug delivery.
- MeSH
- aplikace orální MeSH
- celulosa aplikace a dávkování chemie MeSH
- chemie farmaceutická metody MeSH
- chitosan aplikace a dávkování chemie MeSH
- dospělí MeSH
- kofein aplikace a dávkování chemie MeSH
- kolon metabolismus MeSH
- koncentrace vodíkových iontů MeSH
- lékové formy MeSH
- léky implantované aplikace a dávkování chemie farmakokinetika MeSH
- lidé MeSH
- pomocné látky aplikace a dávkování chemie MeSH
- reprodukovatelnost výsledků MeSH
- rozpustnost MeSH
- sliny metabolismus MeSH
- systémy cílené aplikace léků metody MeSH
- vyprazdňování žaludku účinky léků MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- celulosa MeSH
- chitosan MeSH
- kofein MeSH
- lékové formy MeSH
- léky implantované MeSH
- microcrystalline cellulose MeSH Prohlížeč
- pomocné látky MeSH
UNLABELLED: Diltiazem hydrochloride is an antihypertensive agent which undergoes extensive first pass metabolism making it a possible candidate for buccal delivery. Diltiazem mucoadhesive buccal patches were prepared using HPMC, chitosan, PVP, PVA and carbopol. The physicochemical interactions between diltiazem and the polymers were investigated by FTIR and DSC, results revealed no interaction between drug and polymers. The patches were evaluated for various physicochemical parameters, in vitro release studies and ex vivo permeation through porcine buccal mucosa. Residual solvent content in patches was determined by gas chromatography and are largely below the tolerated limits. The formulations showed an extended release of the drug upto a period of 12 hours during ex vivo permeation and showed non Fickian drug release. Stability of the optimized formulation was investigated as per ICH guidelines and was found to be stable with respect to drug content and ex vivo permeation. KEYWORDS: diltiazem hydrochloride buccal patches residual solvents mucoadhesion in vitro drug release ex vivo permeation.
- MeSH
- adhezivita MeSH
- chemie farmaceutická MeSH
- diltiazem * MeSH
- stabilita léku * MeSH
- systémy cílené aplikace léků MeSH
- techniky in vitro MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- diltiazem * MeSH
We report kinetic studies of therapeutically highly potent polymer-drug conjugates consisting of amphiphilic N-(2-hydroxypropyl) methacrylamide (HPMA)-based copolymers bearing the anticancer drug doxorubicin (Dox). Highly hydrophobic cholesterol moieties as well as the drug were attached to the polymer backbone by a pH-sensitive hydrazone bond. Moreover, the structure of the spacer between the polymer carrier and the cholesterol moiety differed in order to influence the release rate of the hydrophobic moiety, and thus the disintegration of the high-molecular-weight micellar nanoparticle structure. We performed time-dependent SAXS/SANS measurements after changing pH from a typical blood value (pH 7.2) to that of tumor cells (pH 5.0) to characterize the drug release and changes in particle size and shape. Nanoparticles composed of the conjugates containing Dox were generally larger than the drug-free ones. For most conjugates, nanoparticle growth or decay was observed in the time range of several hours. It was established that the growth/decay rate and the steady-state size of nanoparticles depend on the spacer structure. From analytical fitting, we conclude that the most probable structure of the nanoparticles was a core-shell or a core with attached Gaussian chains. We concluded that the spacer structure determined the fate of a cholesterol derivative after the pH jump. Fitting results for 5α-cholestan-3-onecholestan-3-one and cholesteryl-4-oxopentanoate (Lev-chol) implied that cholesterol moieties continuously escape from the core of the nanoparticle core and concentrate in the hydrophilic shell. In contrast, cholest-4-en-3-one spacer prevent cholesterol escaping. Dox moiety release was only observed after a change in pH. Such findings justify the model proposed in our previous paper. Lastly, the cholesteryl 4-(2-oxopropyl)benzoate (Opb-Chol) was a different case where after the release of hydrophobic Opb-Chol moieties, the core becomes more compact. The physicochemical mechanisms responsible for the scenarios of the different spacers are discussed.
- MeSH
- akrylamidy chemie MeSH
- antitumorózní látky aplikace a dávkování MeSH
- časové faktory MeSH
- cholesterol chemie MeSH
- difrakce rentgenového záření MeSH
- doxorubicin aplikace a dávkování MeSH
- hydrofobní a hydrofilní interakce MeSH
- hydrolýza MeSH
- kinetika MeSH
- koncentrace vodíkových iontů MeSH
- kyseliny polymethakrylové chemie MeSH
- maloúhlový rozptyl MeSH
- micely * MeSH
- molekulární struktura MeSH
- neutronová difrakce MeSH
- povrchové vlastnosti MeSH
- systémy cílené aplikace léků * MeSH
- velikost částic MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- akrylamidy MeSH
- antitumorózní látky MeSH
- cholesterol MeSH
- doxorubicin MeSH
- Duxon MeSH Prohlížeč
- kyseliny polymethakrylové MeSH
- methacrylamide MeSH Prohlížeč
- micely * MeSH
The present review focuses on the description of the design, synthesis and physico-chemical and biological evaluation of polymer nanogels. Nanogels are robust swollen cross-linked polymer nanoparticles that can be used as highly efficient and biodegradable carriers for the transport of drugs in controlled drug delivery. In this article, various types of nanogels are described and methods for their preparation discussed. The possibility of using synthesized nanosystems for targeting are reviewed to show the potential of tailored structures to reach either solid tumor tissue or direct tumor cells. Finally, the methods for encapsulation or attachment of biologically active molecules, e.g. drugs, proteins, are described and compared.
- MeSH
- gely MeSH
- lidé MeSH
- nádory farmakoterapie metabolismus MeSH
- nanočástice chemie metabolismus MeSH
- polymery aplikace a dávkování chemická syntéza metabolismus MeSH
- systémy cílené aplikace léků metody trendy MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- gely MeSH
- polymery MeSH
Design, controlled synthesis, physico-chemical and biological characteristics of novel well-defined biodegradable star-shaped copolymers intended for advanced drug delivery is described. These new biocompatible star copolymers were synthesised by grafting monodispersed semitelechelic linear (sL) N-(2-hydroxypropyl)methacrylamide copolymers onto a 2,2-bis(hydroxymethyl)propionic acid (bisMPA)-based polyester dendritic core of various structures. The hydrodynamic diameter of the star copolymer biomaterials can be tuned from 13 to 31 nm and could be adjusted to a given purpose by proper selection of the bisMPA dendritic core type and generation and by considering the sL copolymer molecular weight and polymer-to-core molar ratio. The hydrolytic degradation was proved for both the star copolymers containing either dendron or dendrimer core, showing the spontaneous hydrolysis in duration of few weeks. Finally, it was shown that the therapy with the biodegradable star conjugate with attached doxorubicin strongly suppresses the tumour growth in mice and is fully curative in most of the treated animals at dose corresponding approximately to one fourth of maximum tolerated dose (MTD) value. Both new biodegradable systems show superior efficacy and tumour accumulation over the first generation of star copolymers containing non-degradable PAMAM core.
- Klíčová slova
- Cancer, Doxorubicin, Drug delivery, HPMA, Star-like polymers, bisMPA,
- MeSH
- akrylamidy MeSH
- biokompatibilní materiály * MeSH
- doxorubicin MeSH
- léčivé přípravky * MeSH
- methakryláty MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nosiče léků MeSH
- polymery MeSH
- systémy cílené aplikace léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- akrylamidy MeSH
- biokompatibilní materiály * MeSH
- doxorubicin MeSH
- hydroxypropyl methacrylate MeSH Prohlížeč
- léčivé přípravky * MeSH
- methakryláty MeSH
- N-(2-hydroxypropyl)methacrylamide MeSH Prohlížeč
- nosiče léků MeSH
- polymery MeSH